Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex
Copyright policy )Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex
Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data reveal a novel regulatory mechanism by which Zbtb20 suppresses the acquisition of an isocortical fate during archicortical neurogenesis to ensure commitment to a CA1 pyramidal neuron fate. We further show that the expression pattern of Zbtb20 is evolutionary conserved in the fetal human hippocampus, where it is complementary to the expression pattern of the Zbtb20 target gene Tbr1. Therefore, the disclosed Zbtb20-mediated transcriptional repressor mechanism may be involved in development of the human archicortex.
- University of Copenhagen Denmark
- University of Southern Denmark Denmark
- University of Copenhagen Denmark
- Odense University Hospital Denmark
Chromatin Immunoprecipitation, hippocampus, Transcription Factors/genetics, Mice, Transgenic, Nerve Tissue Proteins, Inbred C57BL, Hippocampus, Transgenic, Nerve Net/metabolism, Mice, ChIP-Seq, Fetus, Nerve Tissue Proteins/genetics, Animals, Humans, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Pyramidal Cells, Pyramidal Cells/physiology, Gene Expression Regulation, Developmental, Newborn, Mice, Inbred C57BL, Developmental/genetics, Gene Expression Regulation, Animals, Newborn, Hippocampus/cytology, Zbtb20, targetome, Nerve Net, microarray, Gene Expression Regulation, Developmental/genetics, Transcription Factors
Chromatin Immunoprecipitation, hippocampus, Transcription Factors/genetics, Mice, Transgenic, Nerve Tissue Proteins, Inbred C57BL, Hippocampus, Transgenic, Nerve Net/metabolism, Mice, ChIP-Seq, Fetus, Nerve Tissue Proteins/genetics, Animals, Humans, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Pyramidal Cells, Pyramidal Cells/physiology, Gene Expression Regulation, Developmental, Newborn, Mice, Inbred C57BL, Developmental/genetics, Gene Expression Regulation, Animals, Newborn, Hippocampus/cytology, Zbtb20, targetome, Nerve Net, microarray, Gene Expression Regulation, Developmental/genetics, Transcription Factors
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